SEC23A

Summary

SEC23A (SEC23 homolog A, COPII component, HGNC:10701) is a protein-coding gene on chromosome 14q21.1, encoding Protein transport protein Sec23A (Q15436). Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER).

The protein encoded by this gene is a member of the SEC23 subfamily of the SEC23/SEC24 family. It is part of a protein complex and found in the ribosome-free transitional face of the endoplasmic reticulum (ER) and associated vesicles. This protein has similarity to yeast Sec23p component of COPII. COPII is the coat protein complex responsible for vesicle budding from the ER. The encoded protein is suggested to play a role in the ER-Golgi protein trafficking.

Source: NCBI Gene 10484 — RefSeq curated summary.

At a glance

• Gene–disease (curated): craniolenticulosutural dysplasia (Moderate, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 267 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 54
• Druggable target: yes
• MANE Select transcript: NM_006364

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10701
Approved symbol	SEC23A
Name	SEC23 homolog A, COPII component
Location	14q21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000100934
Ensembl biotype	protein_coding
OMIM	610511
Entrez	10484

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 21 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000307712, ENST00000537403, ENST00000545328, ENST00000548032, ENST00000553925, ENST00000553970, ENST00000554615, ENST00000555017, ENST00000555363, ENST00000555425, ENST00000555682, ENST00000556092, ENST00000557280, ENST00000557437, ENST00000625395, ENST00000857740, ENST00000857741, ENST00000857742, ENST00000857743, ENST00000919376, ENST00000945648, ENST00000945649, ENST00000945650, ENST00000945651, ENST00000945652

RefSeq mRNA: 1 — MANE Select: NM_006364 NM_006364

CCDS: CCDS9668

Canonical transcript exons

ENST00000307712 — 20 exons

Exon	Start	End
ENSE00000656375	39040732	39040887
ENSE00000656378	39048652	39048729
ENSE00000656381	39061765	39061871
ENSE00000656382	39063324	39063413
ENSE00000656383	39064913	39064993
ENSE00000656384	39067173	39067296
ENSE00000656385	39074415	39074530
ENSE00000889764	39042786	39042872
ENSE00000889765	39045163	39045324
ENSE00000889767	39055143	39055296
ENSE00000889773	39075935	39076093
ENSE00000889778	39095898	39096139
ENSE00001375759	39103032	39103235
ENSE00001665685	39085762	39085906
ENSE00003475365	39091477	39091713
ENSE00003507841	39039031	39039096
ENSE00003517596	39092541	39092627
ENSE00003550467	39093187	39093244
ENSE00003585999	39031919	39033328
ENSE00003623209	39086929	39087008

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 99.29.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 69.9978 / max 443.1959, expressed in 1823 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143011	62.2292	1822
143010	5.9898	1471
207203	1.2742	802
143006	0.5047	192

Top tissues by expression

302 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	99.29	gold quality
jejunum	UBERON:0002115	98.39	gold quality
blood vessel layer	UBERON:0004797	98.05	gold quality
tibia	UBERON:0000979	97.99	gold quality
stromal cell of endometrium	CL:0002255	97.85	gold quality
calcaneal tendon	UBERON:0003701	97.45	gold quality
seminal vesicle	UBERON:0000998	97.21	gold quality
saphenous vein	UBERON:0007318	97.20	gold quality
parietal pleura	UBERON:0002400	97.02	gold quality
smooth muscle tissue	UBERON:0001135	96.98	gold quality
superficial temporal artery	UBERON:0001614	96.90	gold quality
cauda epididymis	UBERON:0004360	96.83	gold quality
adrenal tissue	UBERON:0018303	96.83	gold quality
heart right ventricle	UBERON:0002080	96.78	gold quality
synovial joint	UBERON:0002217	96.71	gold quality
urethra	UBERON:0000057	96.46	gold quality
duodenum	UBERON:0002114	96.46	gold quality
pleura	UBERON:0000977	96.41	gold quality
colonic epithelium	UBERON:0000397	96.33	gold quality
visceral pleura	UBERON:0002401	96.33	gold quality
germinal epithelium of ovary	UBERON:0001304	96.32	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.31	gold quality
biceps brachii	UBERON:0001507	96.19	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.09	gold quality
vena cava	UBERON:0004087	96.07	gold quality
tendon	UBERON:0000043	95.93	gold quality
pericardium	UBERON:0002407	95.86	gold quality
cartilage tissue	UBERON:0002418	95.64	gold quality
skin of hip	UBERON:0001554	95.41	gold quality
popliteal artery	UBERON:0002250	95.37	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.11
E-CURD-135	no	987.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

168 targeting SEC23A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478

Literature-anchored findings (GeneRIF, showing 20)

• When entering into mitosis, the COPII component Sec24Cp is simultaneously deglycosylated and phosphorylated; however, Sec23A is not. (PMID:15013749)
• Sec23A mutation causes cranio-lenticulo-sutural dysplasia, and disrupts the nucleation of COPII coat proteins at endoplasmic reticulum exit sites. (PMID:17981133)
• Data show that coupling of the Sec23/24 and Sec13/31 layers of the COPII coat is required to drive export of collagen from the endoplasmic reticulum, and that efficient COPII assembly is essential for normal craniofacial development during embryogenesis. (PMID:18713835)
• Sec23A overexpression reduced cell growth but did not induce apoptosis, whereas inhibition of Sec23A stimulated cell proliferation (PMID:21593139)
• the BBF2H7-mediated Sec23A pathway is required for ER-to-Golgi procollagen trafficking to promote collagen synthesis (PMID:22495181)
• Hypomorphic mutations of SEC23B gene account for mild phenotypes of congenital dyserythropoietic anemia type II. (PMID:23453696)
• Data indicate that a synthetic polypeptide containing the N terminus of bovine AE1 bound the Sec23A-Sec24C complex through a selective interaction with Sec24C. (PMID:23658022)
• show that membrane association of COPII components, and in particular of Sec23a, is impaired by ER stress-inducing agents suggesting the existence of a dynamic interplay between protein folding and COPII assembly at the ER (PMID:23994533)
• ALG-2 attenuates COPII budding in vitro and stabilizes the Sec23/Sec31A complex. (PMID:24069399)
• Data indicate that vesicular transport protein SEC23A as a target of miR-375. (PMID:27036030)
• findings suggest that miR-21 promoted proliferation, migration, and invasion of colorectal cancer cells in vitro by down regulating the expression of Sec23A (PMID:27495250)
• miR-375 is involved in development of chemo-resistance to docetaxel through regulating SEC23A and YAP1 expression. (PMID:27832783)
• Mutation on serine207 of Sec23A protein changes Unc-51 like kinase 1(ULK 1) targeted phosphorylation. During elevated autophagy, induced by amino acid starvation, rapamycin, or overexpression of ULK1,phosphorylation of Sec23A reduced the interaction between vesicular transport proteins Sec23A and Sec31A. (PMID:28486929)
• This larger GWAS yields two loci harboring genome-wide significant variants affecting serum 25-hydroxyvitamin D levels (P = 4.7x10(-9) at rs8018720 in SEC23A, and P = 1.9x10(-14) at rs10745742 in AMDHD1). (PMID:29343764)
• Transduction with BBF2H7/CREB3L2 upregulates SEC23A protein in erythroblasts and partially corrects the hypo-glycosylation phenotype associated with CDAII. (PMID:29536501)
• these data demonstrate an equivalent function for SEC23A/B, with evolutionary shifts in the transcription program likely accounting for the distinct phenotypes of SEC23A/B deficiency within and across species, a paradigm potentially applicable to other sets of paralogous genes. (PMID:30065114)
• identified Sec23a, a gene target of miR-200c, suppresses miR-200c augmented oligometastatic to polymetastatic progression via its secretome. Firstly, miR-200c over-expression and Sec23a interference accelerated oligometastatic to polymetatic progression. Secondly, Sec23a functions downstream of miR-200c. (PMID:30301603)
• MiR-29b-3p Inhibits the Inflammation Injury in Human Umbilical Vein Endothelial Cells by Regulating SEC23A. (PMID:35190931)
• SEC23A confers ER stress resistance in gastric cancer by forming the ER stress-SEC23A-autophagy negative feedback loop. (PMID:37670384)
• Novel compound heterozygous variants of the SEC23A gene in a Chinese family with cranio-lenticulo-sutural dysplasia based on data from a large cohort of congenital cataract patients. (PMID:37828500)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sec23a	ENSDARG00000104230
mus_musculus	Sec23a	ENSMUSG00000020986
rattus_norvegicus	Sec23a	ENSRNOG00000004657
drosophila_melanogaster	Sec23	FBGN0262125
caenorhabditis_elegans		WBGENE00004754

Paralogs (1): SEC23B (ENSG00000101310)

Protein

Protein identifiers

Protein transport protein Sec23A — Q15436 (reviewed: Q15436)

Alternative names: SEC23-related protein A

All UniProt accessions (9): Q15436, F5H365, G3V1W4, G3V2R6, G3V3G5, G3V4Q2, G3V4V1, G3V5K1, G3V5X8

UniProt curated annotations — full annotation on UniProt →

Function. Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER). The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules for their transport to the Golgi complex. Required for the translocation of insulin-induced glucose transporter SLC2A4/GLUT4 to the cell membrane.

Subunit / interactions. COPII is composed of at least five proteins: the Sec23/24 complex, the Sec13/31 complex and Sar1. Interacts with SEC23IP. Interacts with HTR4. Interacts with SEC16A. Interacts with SLC6A4. Interacts (as part of the Sec23/24 complex) with SEC22B; recruits SEC22B into COPII-coated vesicles and allows the transport of this cargo from the endoplasmic reticulum to the Golgi. Interacts (via Gelsolin-like repeat) with MIA2 and MIA3; specifically involved in the transport of large cargos like the collagen COL7A1. Interacts with DDHD1. Interacts with TMEM39A. Interacts with SACM1L; this interaction is reduced in the absence of TMEM39A. Interacts with kinase FAM20C; transport of FAM20C from the endoplasmic reticulum to the Golgi is likely to be mediated by COPII vesicles.

Subcellular location. Cytoplasmic vesicle. COPII-coated vesicle membrane. Endoplasmic reticulum membrane. Cytoplasm. Cytosol.

Tissue specificity. Ubiquitously expressed.

Disease relevance. Craniolenticulosutural dysplasia (CLSD) [MIM:607812] Autosomal recessive syndrome characterized by late-closing fontanels, sutural cataracts, facial dysmorphisms and skeletal defects. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The Gelsolin-like repeat mediates interaction with proteins containing PPP motifs that include MIA2, MIA3 but also SEC31A. These interactions are probably competitive.

Similarity. Belongs to the SEC23/SEC24 family. SEC23 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15436-1	1	yes
Q15436-2	2

RefSeq proteins (1): NP_006355* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006895	Znf_Sec23_Sec24	Domain
IPR006896	Sec23/24_trunk_dom	Domain
IPR006900	Sec23/24_helical_dom	Domain
IPR007123	Gelsolin-like_dom	Domain
IPR012990	Beta-sandwich_Sec23_24	Domain
IPR029006	ADF-H/Gelsolin-like_dom_sf	Homologous_superfamily
IPR036174	Znf_Sec23_Sec24_sf	Homologous_superfamily
IPR036175	Sec23/24_helical_dom_sf	Homologous_superfamily
IPR036180	Gelsolin-like_dom_sf	Homologous_superfamily
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR037364	Sec23	Family
IPR037550	Sec23_C	Domain

Pfam: PF00626, PF04810, PF04811, PF04815, PF08033

UniProt features (91 total): strand 38, helix 30, turn 6, mutagenesis site 4, binding site 4, sequence variant 2, modified residue 2, initiator methionine 1, chain 1, sequence conflict 1, repeat 1, splice variant 1

Structure

Experimental structures (PDB)

29 structures.

PDB	Method	Resolution (Å)
2NUT	X-RAY DIFFRACTION	2.3
5VNL	X-RAY DIFFRACTION	2.39
5VNF	X-RAY DIFFRACTION	2.41
5VNN	X-RAY DIFFRACTION	2.5
9UVG	X-RAY DIFFRACTION	2.54
5VNK	X-RAY DIFFRACTION	2.55
5KYN	X-RAY DIFFRACTION	2.55
5VNG	X-RAY DIFFRACTION	2.6
5VNH	X-RAY DIFFRACTION	2.6
9UVE	X-RAY DIFFRACTION	2.6
5VNE	X-RAY DIFFRACTION	2.7
3EFO	X-RAY DIFFRACTION	2.7
3EGD	X-RAY DIFFRACTION	2.7
5VNM	X-RAY DIFFRACTION	2.77
5VNI	X-RAY DIFFRACTION	2.79
2NUP	X-RAY DIFFRACTION	2.8
5VNJ	X-RAY DIFFRACTION	2.81
5VNO	X-RAY DIFFRACTION	2.9
9UVD	X-RAY DIFFRACTION	2.98
3EG9	X-RAY DIFFRACTION	3
9UVF	X-RAY DIFFRACTION	3.15
5KYW	X-RAY DIFFRACTION	3.2
3EGX	X-RAY DIFFRACTION	3.3
8HR0	X-RAY DIFFRACTION	3.34
5KYY	X-RAY DIFFRACTION	3.4
5KYU	X-RAY DIFFRACTION	3.51
5KYX	X-RAY DIFFRACTION	3.52
2YRC	SOLUTION NMR
2YRD	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15436-F1	92.86	0.85

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 61; 66; 85; 88

Post-translational modifications (2): 2, 308

Mutagenesis-validated functional residues (4):

Position	Phenotype
628	decreased interaction with mia3; when associated with a-681.
672	decreased interaction with mia3; when associated with a-678.
678	decreased interaction with mia3; when associated with k-672.
681	decreased interaction with mia3; when associated with a-628.

Function

Pathways and Gene Ontology

Reactome pathways

25 pathways

ID	Pathway
R-HSA-1655829	Regulation of cholesterol biosynthesis by SREBP (SREBF)
R-HSA-204005	COPII-mediated vesicle transport
R-HSA-2132295	MHC class II antigen presentation
R-HSA-5694530	Cargo concentration in the ER
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-983170	Antigen Presentation: Folding, assembly and peptide loading of class I MHC
R-HSA-1280218	Adaptive Immune System
R-HSA-1430728	Metabolism
R-HSA-1643685	Disease
R-HSA-168256	Immune System
R-HSA-199977	ER to Golgi Anterograde Transport
R-HSA-199991	Membrane Trafficking
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-556833	Metabolism of lipids
R-HSA-5653656	Vesicle-mediated transport
R-HSA-5663205	Infectious disease
R-HSA-597592	Post-translational protein modification
R-HSA-8957322	Metabolism of steroids
R-HSA-948021	Transport to the Golgi and subsequent modification
R-HSA-9679506	SARS-CoV Infections
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9705683	SARS-CoV-2-host interactions
R-HSA-9824446	Viral Infection Pathways
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 317 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_ANTIGEN_PRESENTATION_FOLDING_ASSEMBLY_AND_PEPTIDE_LOADING_OF_CLASS_I_MHC, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GOBP_VESICLE_ORGANIZATION, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, TOMLINS_PROSTATE_CANCER_DN, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_ENDOPLASMIC_RETICULUM_TO_GOLGI_VESICLE_MEDIATED_TRANSPORT, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, ATF1_Q6, GOCC_COATED_VESICLE, GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_DN, GOCC_VESICLE_COAT

GO Biological Process (7): intracellular protein transport (GO:0006886), protein localization to plasma membrane (GO:0072659), COPII-coated vesicle cargo loading (GO:0090110), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), protein transport (GO:0015031), vesicle-mediated transport (GO:0016192), COPII-coated vesicle budding (GO:0090114)

GO Molecular Function (4): GTPase activator activity (GO:0005096), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (12): Golgi membrane (GO:0000139), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), ER to Golgi transport vesicle membrane (GO:0012507), COPII vesicle coat (GO:0030127), perinuclear region of cytoplasm (GO:0048471), endoplasmic reticulum exit site (GO:0070971), cytoplasm (GO:0005737), membrane (GO:0016020), COPII-coated ER to Golgi transport vesicle (GO:0030134), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
ER to Golgi Anterograde Transport	2
Metabolism of steroids	1
Adaptive Immune System	1
SARS-CoV-2-host interactions	1
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Membrane Trafficking	1
Transport to the Golgi and subsequent modification	1
Vesicle-mediated transport	1
Post-translational protein modification	1
Metabolism	1
Disease	1
Metabolism of proteins	1
Metabolism of lipids	1
Asparagine N-linked glycosylation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	5
cellular anatomical structure	5
intracellular transport	3
intracellular protein localization	2
transport	2
protein transport	1
protein localization to membrane	1
protein localization to cell periphery	1
vesicle cargo loading	1
COPII-coated vesicle budding	1
intercellular transport	1
Golgi vesicle transport	1
establishment of protein localization	1
cellular process	1
endoplasmic reticulum to Golgi vesicle-mediated transport	1
vesicle budding from membrane	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
transition metal ion binding	1
binding	1
cation binding	1
Golgi apparatus	1
bounding membrane of organelle	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
COPII-coated ER to Golgi transport vesicle	1
transport vesicle membrane	1
coated vesicle membrane	1
ER to Golgi transport vesicle membrane	1
vesicle coat	1
endoplasmic reticulum	1
intracellular anatomical structure	1
coated vesicle	1
intracellular vesicle	1

Protein interactions and networks

STRING

1970 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEC23A	SEC31A	O94979	979
SEC23A	SEC13	P55735	931
SEC23A	SEC16A	O15027	906
SEC23A	SAR1A	Q9NR31	903
SEC23A	SEC24B	O95487	854
SEC23A	PREB	Q9HCU5	827
SEC23A	MIA3	Q5JRA6	827
SEC23A	SAR1B	Q9Y6B6	816
SEC23A	GOLPH3	Q9H4A6	794
SEC23A	SEC16B	Q96JE7	793
SEC23A	SEC24A	O95486	791
SEC23A	LMAN1	P49257	789
SEC23A	TRAPPC3	O43617	738
SEC23A	AMDHD1	Q96NU7	716
SEC23A	SEC24D	O94855	708

IntAct

228 interactions, top by confidence:

A	B	Type	Score
SEC23A	SEC24C	psi-mi:“MI:0407”(direct interaction)	0.810
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
SEC23A	SEC23B	psi-mi:“MI:0915”(physical association)	0.670
SEC23A	SEC23IP	psi-mi:“MI:0915”(physical association)	0.670
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
SEC23A	CDK16	psi-mi:“MI:0915”(physical association)	0.580
CDK16	SEC23A	psi-mi:“MI:0915”(physical association)	0.580
SS18L2	SMARCA2	psi-mi:“MI:0914”(association)	0.570
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
SEC23A	GJA8	psi-mi:“MI:0915”(physical association)	0.560
SEC23A	TMEM45B	psi-mi:“MI:0915”(physical association)	0.560
FASLG	SEC23A	psi-mi:“MI:0915”(physical association)	0.560
DNM2	SEC23A	psi-mi:“MI:0915”(physical association)	0.560
SEC23A	SF1	psi-mi:“MI:0915”(physical association)	0.560
PIAS2	SEC23A	psi-mi:“MI:0915”(physical association)	0.560
SEC23A	FATE1	psi-mi:“MI:0915”(physical association)	0.560
SEC23A	SUCLA2	psi-mi:“MI:0915”(physical association)	0.560
SEC23A	MINAR1	psi-mi:“MI:0915”(physical association)	0.560
SEC23A	MFF	psi-mi:“MI:0915”(physical association)	0.560
ERLIN1	SEC23A	psi-mi:“MI:0915”(physical association)	0.560
SEC23A	CLEC17A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (317): SEC23A (Affinity Capture-MS), SEC23A (Affinity Capture-MS), ARMC1 (Co-fractionation), SEC13 (Co-fractionation), SEC23A (Co-fractionation), SEC23A (Co-fractionation), SEC23A (Co-fractionation), SEC23A (Co-fractionation), SEC23A (Co-fractionation), SEC23A (Co-fractionation), SEC23B (Co-fractionation), SEC24A (Co-fractionation), SEC24B (Co-fractionation), SUMO3 (Co-fractionation), SEC23A (Affinity Capture-MS)

ESM2 similar proteins: A2VDL8, A7YWS7, O35142, O54956, O55029, O70133, O88544, O94973, O95782, P17426, P17427, P18484, P35605, P35606, P38024, P48444, P53619, P56282, Q01405, Q05AS9, Q08211, Q0VCK5, Q15436, Q15437, Q28141, Q3SZA0, Q3SZN2, Q41141, Q4R4I8, Q5E9U9, Q5F418, Q5R5G2, Q5R664, Q5R874, Q5R9P3, Q5RA77, Q5XJY5, Q5ZK03, Q5ZKQ6, Q5ZL57

Diamond homologs: A1CRW7, A1D4S4, A2Q8L1, A2VDL8, A3GFA2, A4R1J7, A5DA00, A5E7S3, O74873, O94672, P0CR38, P0CR39, P15303, Q01405, Q05AS9, Q0CUU1, Q0US25, Q15436, Q15437, Q1DY01, Q2HB00, Q2URM9, Q3SZN2, Q4PE39, Q4WK80, Q54T59, Q5A455, Q5BGR9, Q5R5G2, Q5R9P3, Q5ZK03, Q6BQT6, Q6C5L5, Q6CPH3, Q6FSI6, Q6FSK3, Q758M7, Q7SZE5, Q84WI4, Q8H0S3

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
SEC23A	“form complex”	“COPII vesicle”	binding
SEC23IP	“up-regulates activity”	SEC23A	binding
SAR1A	“up-regulates quantity”	SEC23A	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 142 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	6	22.5×	3e-05
Cargo concentration in the ER	6	19.2×	5e-05
EPHA-mediated growth cone collapse	5	18.1×	5e-04
EPH-ephrin mediated repulsion of cells	7	14.6×	4e-05
COPII-mediated vesicle transport	8	12.4×	3e-05
COPI-dependent Golgi-to-ER retrograde traffic	11	11.6×	7e-07
COPI-mediated anterograde transport	11	11.5×	7e-07
Signaling by ALK fusions and activated point mutants	8	11.4×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
COPII-coated vesicle cargo loading	6	47.2×	7e-07
peptidyl-tyrosine phosphorylation	7	23.4×	3e-06
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	7	18.7×	1e-05
endoplasmic reticulum to Golgi vesicle-mediated transport	17	18.3×	5e-14
ephrin receptor signaling pathway	6	16.4×	1e-04
cell surface receptor protein tyrosine kinase signaling pathway	11	15.2×	9e-08
mitophagy	6	15.1×	2e-04
autophagosome maturation	5	13.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

267 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	131
Likely benign	54
Benign	58

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1228	NM_006364.4(SEC23A):c.1144T>C (p.Phe382Leu)	Pathogenic
1686940	NM_006364.4(SEC23A):c.1795G>A (p.Glu599Lys)	Likely pathogenic
931175	NM_006364.4(SEC23A):c.1227+2T>G	Likely pathogenic

SpliceAI

3312 predictions. Top by Δscore:

Variant	Effect	Δscore
14:39039097:C:CC	acceptor_gain	1.0000
14:39039098:T:C	acceptor_gain	1.0000
14:39040728:TTA:T	donor_loss	1.0000
14:39040729:TAC:T	donor_loss	1.0000
14:39040730:A:AC	donor_gain	1.0000
14:39040730:AC:A	donor_gain	1.0000
14:39040730:ACC:A	donor_loss	1.0000
14:39040731:C:A	donor_loss	1.0000
14:39040731:C:CG	donor_gain	1.0000
14:39040731:CC:C	donor_gain	1.0000
14:39040731:CCT:C	donor_gain	1.0000
14:39040731:CCTG:C	donor_gain	1.0000
14:39040731:CCTGG:C	donor_gain	1.0000
14:39040883:ATGGT:A	acceptor_gain	1.0000
14:39040884:TGGT:T	acceptor_gain	1.0000
14:39040885:GGT:G	acceptor_gain	1.0000
14:39040886:GT:G	acceptor_gain	1.0000
14:39040888:C:CC	acceptor_gain	1.0000
14:39040891:A:AC	acceptor_gain	1.0000
14:39040892:T:C	acceptor_gain	1.0000
14:39040892:T:TC	acceptor_gain	1.0000
14:39040893:T:C	acceptor_gain	1.0000
14:39040893:T:TC	acceptor_gain	1.0000
14:39040894:T:C	acceptor_gain	1.0000
14:39040894:T:TC	acceptor_gain	1.0000
14:39045157:TCTTA:T	donor_loss	1.0000
14:39045158:CTTAC:C	donor_loss	1.0000
14:39045159:TTAC:T	donor_loss	1.0000
14:39045160:TAC:T	donor_loss	1.0000
14:39045162:CCT:C	donor_gain	1.0000

AlphaMissense

5023 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:39033258:G:T	A760D	1.000
14:39033261:A:G	L759P	1.000
14:39033270:A:C	L756W	1.000
14:39033270:A:G	L756S	1.000
14:39033274:G:C	H755D	1.000
14:39033281:A:C	F752L	1.000
14:39033281:A:T	F752L	1.000
14:39033282:A:C	F752C	1.000
14:39033282:A:G	F752S	1.000
14:39033283:A:G	F752L	1.000
14:39033283:A:T	F752I	1.000
14:39033293:A:C	S748R	1.000
14:39033293:A:T	S748R	1.000
14:39033295:T:G	S748R	1.000
14:39033301:C:G	D746H	1.000
14:39033304:C:G	D745H	1.000
14:39033306:G:A	T744I	1.000
14:39039070:G:C	N723K	1.000
14:39039070:G:T	N723K	1.000
14:39039074:A:T	V722D	1.000
14:39039086:A:G	L718P	1.000
14:39039086:A:T	L718H	1.000
14:39039088:G:C	F717L	1.000
14:39039088:G:T	F717L	1.000
14:39039090:A:G	F717L	1.000
14:39040823:A:G	L684P	1.000
14:39040875:A:G	W667R	1.000
14:39040875:A:T	W667R	1.000
14:39042821:C:G	D651H	1.000
14:39042826:A:G	L649P	1.000

dbSNP variants (sampled 300 via entrez): RS1000078363 (14:39051287 G>T), RS1000094632 (14:39031596 AAACAACAAC>A,AAACAAC,AAACAACAACAAC), RS1000103970 (14:39054655 CAG>C), RS1000224079 (14:39084392 C>A), RS1000264682 (14:39081664 G>T), RS1000299853 (14:39097824 C>G), RS1000356316 (14:39102557 T>C), RS1000357177 (14:39035294 TAAGA>T), RS1000366990 (14:39034897 C>T), RS1000373185 (14:39098019 G>A), RS1000461123 (14:39072186 C>T), RS1000481003 (14:39067559 G>A,C,T), RS1000490726 (14:39072031 C>T), RS1000584970 (14:39048939 A>G,T), RS1000600423 (14:39092223 T>A,C)

Disease associations

OMIM: gene MIM:610511 | disease phenotypes: MIM:607812

GenCC curated gene-disease

Disease	Classification	Inheritance
craniolenticulosutural dysplasia	Moderate	Autosomal recessive

Mondo (1): craniolenticulosutural dysplasia (MONDO:0011911)

Orphanet (1): Craniolenticulosutural dysplasia (Orphanet:50814)

HPO phenotypes

54 total (30 of 54 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000154	Wide mouth
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000233	Thin vermilion border
HP:0000239	Large fontanelles
HP:0000256	Macrocephaly
HP:0000260	Wide anterior fontanel
HP:0000272	Malar flattening
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000327	Hypoplasia of the maxilla
HP:0000336	Prominent supraorbital ridges
HP:0000343	Long philtrum
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000445	Wide nose
HP:0000463	Anteverted nares
HP:0000565	Esotropia
HP:0000648	Optic atrophy
HP:0000670	Carious teeth
HP:0000684	Delayed eruption of teeth
HP:0000685	Hypoplasia of teeth
HP:0000691	Microdontia
HP:0000750	Delayed speech and language development
HP:0000774	Narrow chest
HP:0000938	Osteopenia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005367_2	Vitamin D levels	1.000000e-11
GCST009391_1331	Metabolite levels	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010361	lysophosphatidylcholine 18:2 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C564332	Craniolenticulosutural Dysplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295827 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.38	Kd	4180	nM	CHEMBL3752910
5.38	ED50	4180	nM	CHEMBL3752910
5.31	Kd	4905	nM	CHEMBL5653589
5.31	ED50	4905	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 5 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149363: Binding affinity to human SEC23A incubated for 45 mins by Kinobead based pull down assay	kd	4.1796	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149363: Binding affinity to human SEC23A incubated for 45 mins by Kinobead based pull down assay	kd	4.9052	uM

CTD chemical–gene interactions

45 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, increases expression	3
Acetaminophen	decreases expression	3
Tobacco Smoke Pollution	increases expression, increases methylation, affects expression	3
Air Pollutants	affects expression, increases abundance, decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
arsenite	decreases reaction, affects binding	1
sodium arsenite	increases expression	1
ciglitazone	affects binding, increases expression	1
cyanoginosin LR	decreases expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects expression, affects reaction	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
bisphenol B	increases expression	1
abrine	decreases expression, increases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	decreases expression	1
Benztropine	affects cotreatment, increases expression	1
Caffeine	decreases expression	1
Cuprizone	increases expression, affects cotreatment	1
Doxorubicin	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Fluorouracil	affects response to substance	1
Furaldehyde	affects cotreatment, decreases expression, affects localization	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4119023	Binding	Binding affinity to SEC23A in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TK36	HAP1 SEC23A (-) 1	Cancer cell line	Male
CVCL_TK37	HAP1 SEC23A (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.